Yellow fever outbreaks in South America: Current epidemiology, legacies of the recent past and perspectives for the near future

Yellow fever (YF) is an acute, potentially fatal, viral illness and remains a global threat, especially in endemic regions such as Africa and South America. Two types of outbreaks and scenarios are well-defined: YF in Africa and YF in the Americas. In Africa, where YF originated, the vectors and most simian species have more resistance to YF infection and rarely develop the disease; therefore, they are tolerable to the immune response to YF [[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27]].

In the Americas region, the sylvatic cycle is associated with the vectors Haemagogus and Sabethes while in the urban cycle development is due to humans' eventual infection and transmission by Aedes species. However, there are limitations of vector competence testing for Aedes aegypti in assessing yellow fever virus transmission. Some studies highlight geographic variability, alternative vectors, environmental influences, co-infections, Wolbachia bacteria, and vaccination strategies as key factors affecting accuracy. There is a need for virus-specific testing parameters rather than a standardized approach for all arboviruses [27].

In South America, where YF virus transmission has been associated mostly with the sylvatic cycle, non-human primates (NHP) are more susceptible to infection by the virus. Therefore, Neotropical species of monkeys are prone to developing fatal infections and epizootic outbreaks are expected to occur in outbreaks in contrast to African settings [2].

In 2024, 61 human cases of yellow fever were confirmed in the Americas Region, of which 30 were fatal. These cases were distributed among five countries: the Plurinational State of Bolivia, Brazil, Colombia, Guyana, and Peru. Bolivia reported eight cases, including four fatal cases; Brazil reported eight cases, including four fatal cases; Colombia reported 23 cases, 13 fatal cases; Guyana reported three cases; and Peru reported 19 cases, including nine deaths (Fig. 1) [3]. In Colombia, although early in 2024 an outbreak in the South of the country raised concerns regarding yellow fever in the Putumayo department, the Ministry of Health did not significantly increase vaccination, and vaccination coverage remained under ideal levels with the consequences of more outbreaks in other departments of Colombia [26].

Fig. 1.

Yellow fever in South America. A. Cases by country, year, and epidemiological week of symptom onset in the Americas Region, 2024 and as of Epidemiological Week 4 of 2025 (Includes only cases for which symptom onset information is available by epidemiological week. B. Municipalities with confirmed cases in humans in Bolivia, Brazil, Colombia, Guyana, and Peru, years 2022–2025 (as of Epidemiological Week 4) (For Brazil, also epizootic information is included) (https://www.paho.org/sites/default/files/2025-02/2025-feb-3-phe-epi-alert-yellow-feverenfinal.pdf) [3].

The recent Pan American Health Organization (PAHO) alert in February 2025 rekindled concerns regarding yellow fever cases in South America. It raised questions about the potential regional and global implications. Between epidemiological weeks 1 and 4 of 2025, autochthonous cases were reported in Brazil (8 cases, 4 deaths), Colombia (8 cases, two deaths) and Peru (1 fatal case) (Fig. 1) [3].

In 2025, however, cases have been concentrated mainly in the state of São Paulo in Brazil and the department of Tolima in Colombia, regions outside the Amazon region of both countries (Fig. 1) [3]. The outbreak in Tolima, Colombia, is highly concerning. It started in October 2024 and up to March 5, 2025, includes 37 confirmed cases of yellow fever, 32 men, aged 13-80 y, and 5 women, aged 11-89 y. The cases are concentrated in rural areas, so it is considered a jungle-based outbreak, with no confirmed cases originating in urban areas. Fifteen deaths have been recorded (case fatality rate of 40.5%) (https://www.ins.gov.co/buscador-eventos/BoletinEpidemiologico/2025_Boletin_epidemiologico_semana_9.pdf). As of March 8, 2025, considering the period between July 2024 and March 2025, Brazil had 45 confirmed human cases of yellow fever (21 fatal), 24 cases in the state of São Paulo, 4 in Minas Gerais, 1 in Tocantins and 16 in Pará (https://www.gov.br/saude/pt-br/assuntos/saude-de-a-a-z/a/arboviroses/informe-semanal/2025/informe-semanal-no-03.pdf/@@download/file).

However, cases of the disease had already been occurring, and the need to intensify preventive measures had been justified for some time. In the context of significant YF risk, important actions are indicated particularly heightened epidemiological surveillance to document occurrence and allow for mitigation of YF impact, not only in Brazil but also in other countries in Latin America.

From time to time, the virus re-emerges in the regions outside the Amazon, with outbreaks of varying magnitude and extent, as well as expansion of the areas of viral circulation that can affect all regions of the country. The occurrence is seasonal, with a higher incidence between December and May, when environmental, climatic and epidemiological conditions are favourable to the transmission of the virus, with high temperatures and rainfall and a high density of vectors. The occurrence of outbreaks is generally associated with non-endemic areas with low sensitivity for the surveillance of epizootics in non-human primates (NHP) and with low vaccination coverage (or with pockets of susceptible individuals).

In Brazil, it can be understood that the current epidemiological scenario originated in 2023 with epizootics in NHP and human cases have been observed again and are frequently reported [4]. Throughout 2024, the country reported 8 cases, with four deaths. In Colombia, the scenario has proven to be even more worrying. During 2024, 23 cases were reported, 13 of which were fatal [3]. In this context, although the number of human cases of yellow fever, for now, still does not compare to the frightening scenario observed in Brazil between 2017 and 2018, when in the 2016/2017 and 2017/2018 seasons, 778 cases and 1376 cases were confirmed [5], respectively.

Some lessons and legacies observed in the last epidemic cannot be forgotten, such as incorporating the YF vaccine into the routine vaccination schedule throughout Brazil. It is certain that a potentially significant proportion of the population, including those living in areas at risk with an active sylvatic cycle, has not yet been immunized, which implies a potential increase in the number of cases, including deaths, associated with the disease. Furthermore, areas with vaccination coverage that are potentially below the protective coverage rates and with low homogeneity are at potential risk for outbreaks and, worryingly, for introducing the virus into urban areas.

However, in the current scenario, just as important, if not more important, than raising awareness among the population in countries with transmission of the virus about the need for vaccination is the rapid adaption, in the very short term, of active search and vaccination actions for people living at risk in rural areas and forests where the sylvatic cycle of the disease involving the vectors Haemagogus and Sabethes already exists or may occur.

One of the legacies of the yellow fever epidemic between 2017 and 2018 in Brazil was the information obtained from the surveillance of epizootics in non-human primates and the adoption of models to predict transmission corridors to contribute to decision-making on alert and prevention actions with immunisation [6]. Another legacy was intensifying vaccination in areas with a greater probability of introduction of the virus, managing stocks of doses, and distributing the vaccine to the places and populations at greatest risk at that time.

It should be noted, however, that the models used in 2017 and 2018 were constructed from the monitoring of epizootics in non-human primates, mainly howler monkeys of the genus Alouatta ssp, a species extremely vulnerable to the yellow fever virus. There is evidence that the populations of these monkeys have been seriously reduced or even eliminated in some areas [7]. Currently, this would influence, for example, the sensitivity for detecting epizootics, an essential element for the prediction model.

It cannot be ruled out that the climate changes, as the high temperatures recorded in 2023 and 2024 observed in the affected areas, may, to some degree, contribute to more significant vector activity and dispersion and, therefore, also limit, in some way, the calibration and prediction of the models used in 2017–2018 to assess the dispersion trend in 2025 [8].

The issues related to the use of fractional doses of the yellow fever vaccine during an outbreak scenario deserve attention; a situation in which it is necessary to vaccinate a large number of people in a short period, but with a sufficient number of doses of yellow fever vaccine available.

As observed in Brazil and some African countries [[9], [10], [11]], adapting fractional doses in the context of outbreaks and limited supplies [12] quickly protected millions of people and allowed outbreaks to be controlled [13,14]. However, cases of yellow fever in people vaccinated even with the full dose have been reported [15], which raises questions about where, when and under what circumstances people who previously received (years ago) only a fractional dose of the vaccine should be revaccinated with a full dose [16].

People living in or who will travel to (including local or international travellers) areas at risk of transmission and, above all, with evidence of recently documented circulation, should be a candidate group for prioritisation for (and recommended) revaccination with a full dose [[10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25]]. Despite the recent increases in yellow fever cases in parts of South America, particularly in Brazil, Bolivia, Colombia, Guyana, and Peru during 2024 and early 2025, there have been no reported cases of yellow fever among travelers returning to North America and Europe. This highlights the critical importance of vaccination for individuals traveling to areas where yellow fever is endemoepidemic. In 2018, 13 travel-related cases were reported in EU/EEA countries (https://www.ecdc.europa.eu/sites/default/files/documents/yellow-fever-annual-epidemiological-report-2018.pdf). Even in the south of South America, in not endemic areas, this is important to consider. In Argentina, no cases have been reported among travelers since 2018, and local transmission has been reported since 2009 (https://www.argentina.gob.ar/sites/default/files/2025/01/ben_746_se_9_1332025.pdf). Also Chile have reported few imported cases in the last decade (https://www.clinicasdechile.cl/noticias/ministerio-de-salud-confirma-primer-caso-sospechoso-de-fiebre-amarilla-en-chile/).

Therapeutic plasma exchange (TPE) shows promise in reducing mortality from severe yellow fever (YF)-associated acute liver failure (ALF), as evidenced by an 84 % mortality reduction in an observational study. Intensive TPE significantly decreased ammonia levels and viral loads, enhancing patient survival. However, access to TPE remains limited in South American regions where YF is prevalent, primarily due to high costs and scarce specialized healthcare infrastructure. Expanding TPE availability could be crucial in mitigating YF-associated mortality in endemic areas. Further studies are needed to validate its broader implementation [25].

Another point that deserves emphasis and attention is the awareness of healthcare professionals and the surveillance system for early suspicion, immediate notification and qualified investigation of suspected cases of yellow fever. Particularly in scenarios of simultaneous occurrence with large dengue epidemics, in which cases or deaths are incriminated as severe dengue, or in endemic areas in Brazil for other diseases that may present as icteric and hemorrhagic fever syndromes such as rickettsiosis, leptospirosis and malaria caused by Plasmodium falciparum (in Brazilian Amazon) in which cases could have yellow fever as a differential diagnosis.

Finally, considering the high mobility of travellers to countries with recent or active transmission of yellow fever, the recommendation for timely vaccination should be intensified, not only to prevent the occurrence of cases of the disease among international tourists, as was seen in people who travelled to Brazil during the yellow fever epidemic in 2017–2018 [17], but also to minimise the risk of potential international spread of the virus [18,19] as was observed with Zika, Chikungunya and, more recently, Oropouche [[20], [21], [22], [23]].

It is essential to highlight an internal flow of travellers to several regional countries. In addition, a growing number of African international travellers are arriving in Latin America [24]. This situation highlights the importance of information on the epidemiology of the disease not only for travel medicine practitioners but particularly for public health in all countries with yellow fever transmission in South America.

What to expect regarding yellow fever in 2025 is still uncertain. However, the lessons of the recent past should be considered again so that yellow fever does not become another global challenge soon.

CRediT authorship contribution statement

Rodrigo Nogueira Angerami: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Resources, Visualization, Writing – original draft, Writing – review & editing. Tania Do Socorro Souza Chaves: Conceptualization, Data curation, Investigation, Software, Validation, Writing – original draft, Writing – review & editing. Alfonso J. Rodríguez-Morales: Conceptualization, Data curation, Investigation, Resources, Software, Validation, Writing – original draft, Writing – review & editing.

Funding

The authors did not receive a specific grant from funding agencies in the public, commercial, or not-for-profit sectors to develop this Editorial.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Handling Editor: Patricia Schlagenhauf